What is the treatment for pan-resistant Klebsiella (Klebsiella pneumoniae) infection?

Treatment for Pan-Resistant Klebsiella pneumoniae Infection

For pan-resistant Klebsiella pneumoniae infections, a combination therapy approach with ceftazidime/avibactam or meropenem/vaborbactam as the backbone, potentially combined with another active agent, represents the most effective treatment strategy based on current evidence. 1

First-Line Treatment Options

For KPC-producing Carbapenem-Resistant Klebsiella pneumoniae

• Ceftazidime/avibactam or meropenem/vaborbactam should be used as first-line treatment options when available 1
• These novel β-lactam/β-lactamase inhibitor combinations have demonstrated superior clinical outcomes compared to traditional antibiotic regimens 1
• Ceftazidime/avibactam has shown significantly higher clinical success rates and lower 28-day mortality (18.3% vs 40.8%) compared to other regimens in patients with KPC-producing K. pneumoniae bloodstream infections 1

Alternative Options

• Imipenem/relebactam and cefiderocol may be considered as alternatives when first-line agents are unavailable 1
• For infections susceptible to sulbactam, ampicillin-sulbactam can be considered, particularly for respiratory infections 1

Combination Therapy Approaches

For Severe Infections

• For severe infections caused by CRE susceptible only to polymyxins, aminoglycosides, tigecycline, or fosfomycin, treatment with more than one drug active in vitro is suggested 1
• High-dose tigecycline (100 mg initial dose, followed by 50 mg every 12 hours) combined with colistin has been successfully used to treat pan-resistant K. pneumoniae infections 2
• Double carbapenem therapy (e.g., meropenem plus ertapenem) combined with short-course colistin has shown synergistic and bactericidal effects against pandrug-resistant K. pneumoniae 3

Carbapenem-Based Combinations

• Carbapenem-based combination therapy should be avoided unless the meropenem MIC is ≤8 mg/L, where high-dose extended-infusion meropenem may be used as part of combination therapy 1
• For isolates with meropenem MIC ≤8 mg/L, high-dose extended-infusion carbapenem dosing as part of combination therapy is considered good clinical practice 1

Treatment Considerations for Non-Severe Infections

• For non-severe infections, monotherapy with an in vitro active agent may be considered on an individual basis according to the source of infection 1
• The choice should be guided by the least resistant antibiotic based on MICs relative to the breakpoints 1

Special Considerations

Source Control

• Optimal source control should always be a priority to improve outcomes and potentially shorten antibiotic treatment durations 1
• This is particularly important for pan-resistant infections where antimicrobial options are severely limited 1

Dosing Optimization

• Optimal antibiotic dosing schemes should be used, with attention to adverse effects 1
• Therapeutic drug monitoring should be utilized whenever available 1
• Extended infusions of β-lactams should be considered to optimize pharmacokinetic/pharmacodynamic parameters 1

Monitoring

• Follow-up cultures are recommended in case of treatment failure to detect resistance development 1
• This is especially important when using newer agents like ceftazidime/avibactam, as resistance can develop during treatment 4

Antibiotic Stewardship Considerations

• Extended use of cephalosporins should be discouraged in settings with high incidence of ESBL-producing Enterobacteriaceae 1
• Carbapenems should be preserved and used judiciously due to increasing carbapenem resistance among Enterobacteriaceae 1
• New agents like ceftazidime/avibactam and ceftolozane/tazobactam should be used cautiously until their precise roles are further defined 1

Infection Control Measures

• All patients with carbapenem-resistant Enterobacteriaceae should be managed using contact precautions 1
• Active surveillance cultures should be performed for patients with epidemiologic links to persons from whom CRE have been recovered 1
• In endemic areas, additional strategies to reduce CRE rates should be implemented 1